EQUAL FREQUENCY OF TEL/AML1 ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN WITH AND WITHOUT DOWN SYNDROME

Constitutional trisomy 21 is the most prominent predisposing factor to childhood leukemia, whereas the t(12;21)(p13;q22) with its molecular genetic counterpart, the TEL/AML1 fusion gene, is the most common acquired chromosomal rearrangement in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Thus, it was somewhat surprising that according to the currently available literature the incidence of TEL/AML1+ BCP ALL is extremely low in patients with Down syndrome (DS). To further investigate this issue in a population-based fashion, the authors retrospectively assessed the number of DS patients with a TEL/AML1+ ALL in two consecutive Austrian ALL multicenter trials. Accordingly, they were able to analyze 8 of 10 individuals with DS and a BCP ALL, including 2 who suffered from a TEL/AML1+ leukemia. Based on this observation we concluded that individuals with a constitutional trisomy 21 may have the similar likelihood to develop a TEL/AML1+ leukemia as BCP ALL patients without this specific predisposing factor.     

Verz?gerte Radialisparese nach Monteggia-Fraktur – Ein Fallbericht

Nervensch?digungen als Begleitverletzungen bei Monteggia-Frakturen sind selten und betreffen meistens den N. radialis. üblicherweise kommt es bei frischen Frakturen zu einer spontanen neurologischen Remission, nachdem der Radiuskopf wieder reponiert wurde. Im vorliegenden Fall erlitt ein heute 33-j?hriger Mann eine Parese des N. interosseus posterior 27 Jahre nach einer Monteggia-Fraktur, wobei der Radiuskopf in luxierter Stellung verblieb. Nach einem Bagatelltrauma am Handgelenk beim Federballspielen kam es zu einer L?hmung der Handgelenk- und Fingerstreckmuskulatur. Eine konservative Behandlung mittels intensiver Physiotherapie blieb auch nach 4 Monaten erfolglos. Daraufhin wurde der Nerv exploriert. Der Profundusast zeigte sich dabei narbig adh?rent im Bereich einer beengenden und verdickten Frohse-Arkade. Anschlie?end erfolgte eine Narbenl?sung sowie Spaltung der Arkade, der Radiuskopf wurde im ursprünglichen verrenkten Zustand belassen. Eine v?llige Erholung des l?dierten Nerven war 9 Monate postoperativ erreicht.     

MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of Ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration.

This study reports on the specific expression of the MIC2 gene, a pseudoautosomal gene located on the short arms of the X and Y chromosomes, on Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumor (pPNET) cells. The gene product, a cell membrane protein, is recognized by the newly established monoclonal antibody (MoAb) HBA-71 and the previously described MoAb 12E7 and RFB-1. Furthermore, the reaction pattern of the MIC2 antibodies, especially HBA-71, with normal tissues and a great number of benign and malignant tumors (70 different tumors, 199 tumor samples), as well as the correlation between the specific chromosomal aberrations, i.e., the t(11;22) and the del(22) and the expression of this antigen, are demonstrated. Both ES and pPNET cells express the MIC2 gene in very high amounts, which represents a highly selective and almost unique feature of these cells, making an assignment of these tumors in one entity even more likely. The MIC2 antibodies are of great value for clinical and research purposes.     

Allogene Stammzelltransplantation bei Migranten mit nichtmalignen Krankheiten

Over the last century, immigration has increased substantially in Germany, Austria and Switzerland, as well as in other European countries. Between 9% and 10% of the population consists of migrant families. Due to specific cultural (consanguineous marriages) and ethnic (prevalence of certain genetic and hematologic diseases) characteristics, 20–30% of the children undergoing allogeneic stem cell transplantation for inborn errors come from migrant families. Reduced donor availability, cultural and language barriers, lower socioeconomic background and potentially increased infectious preload are substantial risk factors for disease and therapy related complications. In addition to the effort to motivate members of ethnic minorities to register as potential volunteer stem cell donors, the improvement of medical and supportive care, taking into account these risk factors, is urgently warranted.     

The prognostic significance of serum alpha 1-fetoprotein in children and adolescents with malignant extracranial non-testicular germ cell tumors]

The cooperative therapy study MAKEI 83/86 included an examination of the prognostic value of the AFP in children and adolescents with extracranial non-testicular yolk sac tumors. The serum AFP values of 72 protocol- and follow-up-patients were documented at diagnosis and up to the ninth month of treatment. 32 of these patients had saccrococcygeal tumors, 27 had tumors of the ovary and 13 suffered from extragonadal germ cell-tumors. 4 children showed progressive disease under initial chemotherapy and 1 patient died of therapy, 10 of 72 patients relapsed. The AFP measurements were plotted on semilogarithmic charts. They were compared to the measurements of healthy children up to the age of 1 year. According to the development of the patients' AFP values compared to the reference curves the following classifications could be made: 1. Patients with a normal AFP-decrease id est 50% in less than or equal to 6 days during the 1st month of therapy: 48/72 patients 2. Patients with slow AFP-decrease: 17/72 patients 3. Patients with transient AFP-decrease: 5/72 patients 4. Patients with no AFP-decrease: 2/72 patients According to Kaplan-Meier life table analysis, patients with a normal AFP-decrease had an event-free survival of 89% +/- 4%, whereas all other patients showed an event-free survival of 63% +/- 10% (p less than 0.05). Regarding primary therapy id est tumor resection or preoperative chemotherapy an equal distribution of the patients among those with a normal and slow AFP-decrease was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amphotericin B serum levels in pediatric bone marrow transplant recipients

We studied amphotericin B (AMB) serum levels (n = 590) in 41 pediatric patients, who underwent allogeneic (21) or autologous (20) bone marrow transplantation (BMT). All patients received AMB orally as part of a total gut decontamination; 30/41 patients (73%) had AMB i.v. either for prophylaxis or therapy of fungal infections. Rapid initial dose escalation of AMB and the infusion over 1 h only were well tolerated by the children. Serum level monitoring allowed AMB long-term treatment safely to be administered in children suffering from transplantation-related complications (veno-occlusive disease of the liver, graft-versus-host disease of the liver). An h.p.l.c. method was used for monitoring AMB serum trough levels to avoid levels exceeding 2 mg/l. One lethal fungal infection was observed in 41 pediatric BMT recipients (2.4%). Rapidly increasing doses of AMB at start of therapy and drug monitoring by h.p.l.c. might help to reduce fungal mortality and renal toxicity by a dose sparing effect in BMT recipients.     

Immunohistochemical detection of VEGF in the bone marrow of patients with acute myeloid leukemia. Correlation between VEGF expression and the FAB category

We studied vascular endothelial growth factor (VEGF) expression in bone marrow sections obtained from 3 healthy donors and 41 patients with acute myeloid leukemia (AML) of various French-American-British (FAB) subtypes by immunohistochemical analysis using an anti-VEGF antibody. In normal bone marrow, the anti-VEGF antibody reacted with myeloid progenitor cells and megakaryocytes but not with erythroid cells or mature granulocytic cells. High levels of VEGF were found in the bone marrow in patients with AML-M1, -M2, -M3, -M4, -M4Eo, and -M5. In these leukemias, the vast majority of myeloblasts (> 90%) expressed VEGF. By contrast, in AML-M0, the percentage of VEGF-positive blasts was lower in most cases (median, 42%), and if at all detectable, these blast cells contained only trace amounts of VEGF. In AML-M3 and -M4Eo, maturing granulocytes failed to express VEGF similar to granulocytes in normal bone marrow. In AML-M6, myeloblasts exhibited VEGF, whereas erythroid cells did not. In AML-M7, blast cells and megakaryocytes were identified as major sources of VEGF. In summary, VEGF expression in the bone marrow is restricted to certain stages of differentiation and maturation of myeloid cells and correlates with the FAB category.     

Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.     

Rapid discrimination of early CD34+ myeloid progenitors using CD45-RA analysis

Mononuclear cells (MNC) isolated by density centrifugation of cord blood and healthy bone marrow, and of peripheral blood (PB) from patients treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF after chemotherapy, were double-stained with anti CD34 monoclonal antibody (MoAb) (8G12) versus anti CD45, CD45-RB, CD45- RO, and CD45-RA, respectively, and analyzed by flow cytometry. In all specimens, CD34+ MNC co-expressed CD45 at a low level and the expression of CD45-RB was similar or slightly higher. Most CD34+ MNC were negative for CD45-RO, a weak coexpression was only seen in some bone marrow (BM) and blood samples. In contrast, CD45-RA could subdivide the CD34+ population into fractions negative, dim (+), and normal positive (++) for these subgroups, and typical staining patterns were observed for the different sources of hematopoietic cells: in BM, most CD34+ MNC were RA++. In PB, their majority was RA++ after G-CSF but RA+ or RA- after GM-CSF. In cord blood, the hematopoietic progenitors were mainly RA-/RO-. Semisolid culture of sorted CD34+ MNC showed that clusters and dispersed (late) colony-forming unit-GM (CFU- GM) originated from 34+/RA++ cells, while the 34+/RA- MNC formed compact and multicentric, both white and red colonies derived from early progenitors. Addition of 20 ng stem cell factor per milliliter of medium containing 34+/RA- cord blood MNC led to a change of many burst- forming unit-erythrocyte (BFU-E) to CFU-mix which was not, at least to this extent, seen in blood and BM. We conclude that early myeloid CD34+ cells are 45+/RA-. Because this population excludes 34+/19+ B cells and 33+ myeloid cells, both of which are RA++, two-color flow cytometric analysis using CD34 and CD45-RA facilitates the characterization and quantification of early myeloid progenitor cells.